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John G. Frelinger, Ph.D.

Contact Information

Phone Numbers

Appointment: (585) 276-3000

Research Labs

Biography

Research

My laboratory has a number of interests united by the common theme of T cell recognition. One focus of research has been the generation and maintenance of effective T cell responses to tumors. It has become apparent that anti-tumor responses can be directed against differentiation antigens. Thus, even with multiple mechanisms of establishing and maintaining tolerance, tolerance is not absolute. We hypothesize that it is possible to direct an effective response against tumors by inducing an autoimmune response to organ-specific antigens. To examine this hypothesis, we will use transgenic mice lines we have developed which specifically express human PSA in the prostate and investigate how this expression affects their ability to generate CTL responses to human PSA using novel immunization strategies. In this light, we have been working on developing novel viral vectors for immunization. Helper free herpes amplicons, plasmid based vectors that have an extremely large coding capacity, are attractive viral vaccine candidates for expressing recombinant proteins in vivo for immunization. The amplicon system has particular promise since it encodes no viral gene products and we have shown it very effectively infects dendritic cells. In collaboration with Edith Lord and in conjunction with Tom Foster's laboratory in the Department of Imaging Sciences, we have devised imaging approaches to look at the early steps in immunization and at the effector T cells generated. These studies will contribute to the rational design of immunotherapy for tumors as well as for HIV. We also believe that many of the techniques and approaches will be applicable to other infectious agents as well. In this regard, we are collaborating with investigators at University of North Carolina to identify T cell epitopes of Francisella tularensis. Francisella tularensis (FT) is a gram negative bacterium that is able to infect a wide range of mammalian hosts. FT has several properties that suggest could be developed as a biological weapon, including its ability to be aerosolized and its low LD50. Indeed, it has been asserted that FT was used as a bioweapon in World War II. Unfortunately relatively little information is available concerning the detailed cellular mechanism of resistance to re-infection either in humans or in experimental animals. However, as expected for a pathogen that grows largely intracellularly, T cells are believed to be a critical component in resistance to reinfection and recovery from primary infection. My laboratory has developed a technique called the TCAD ( the T-Cell antigen discovery technique) to identify and improve T cell epitopes, originally in the context of tumor vaccines. We have recently modified this system to large-scale screens for the identification of T cell epitopes from FT using this system which takes advantage of the tremendously enhanced efficiency particulate antigen cross-priming and a novel reporter system of T cell activation. It is hoped that the identification of the T cell epitopes recognized will yield to a batter understanding of the nature of a protective response and ultimately a defined vaccine.

Credentials

Faculty Appointments

Education

1975
BS with Distinction and Departmental Honors | Stanford University
Biology

1980
PhD | California Institute of Technology
Biochemistry

Awards

2016
Manuel D. Goldman Prize for Excellence in Teaching Medical School

2015
Special Commendation for Teaching-Medical School

2014
Chair Education Committee (AAI)
Sponsor: AAI

2012
Alumni Gold Medal Teaching Award

2011 - 2014
AAI Education Committee
Sponsor: American Association of Immunologists

2002
Special Commendation Teaching-Medical School

2000
Distinguished Speaker
Location: University of Texas at San Antonio

2000
Faculty Speaker, Medical School Class of 2000 Awards Ceremony

1998
Herbert W. Mapstone Prize for Teaching Excellence

1996
Special Commendation Teaching-Medical School

1995
Herbert W. Mapstone Prize for Teaching Excellence

1994
Special Commendation Teaching-Medical School

1991 - 1993
Andrew W. Mellon Deans Teaching Scholar
Sponsor: Excellence in Teaching and Research

1986 - 1988
Junior Faculty Research Award
Sponsor: American Cancer Society

1983 - 1984
American Cancer Society Senior Fellowship, California Division

1981 - 1983
Jane Coffin Childs Fellowship

1975
B.S. with Distinction and Departmental Honors

1971 - 1975
National Merit Scholarship

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Patents

Title: Protease Activated Cytokines
U.S. Serial #: 13/639,006
Filed: Mar 31, 2011
Invented By: JohnFrelinger, BaekKim, JohnPuskas, MarkSullivan

Title: Human Glandular Kallikrein (HK2)-Specific Monoclonal Antibodies that Enhance or Inhibit the Enzymatic Activity of HK2
U.S. Serial #: 10/491,761
Filed: Oct 03, 2002
Invented By: TerrenceFisher, JohnFrelinger, EdithLord, Mary AnnNocera-March

Title: Prostate-Specific Regulatory Nucleic Acid Sequences and Transgenic Non-Human Animals Expressing Prostate Specific Antigen
U.S. Serial #: 09/607,549
Filed: Jun 07, 2001
Invented By: RichardBarth, JohnFrelinger, ChungwenWei

Title: Prostate Specific Regulatory Nucleic Acid Sequences and Transgenic Non-Human Animals Expressing Prostate Specific Antigen
U.S. Serial #: 08/797,722
Filed: Feb 11, 1997
Invented By: RichardBarth, JohnFrelinger, ChungwenWei

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Publications

Journal Articles

5/2016
Mikucki ME, Skitzki JJ, Frelinger JG, Odunsi K, Gajewski TF, Luster AD, Evans SS. "Unlocking tumor vascular barriers with CXCR3: Implications for cancer immunotherapy." Oncoimmunology.. 2016 May 0; 5(5):e1116675. Epub 2016 Feb 11.

9/2015
Skrombolas D, Wylie I, Maharaj S, Frelinger JG. "Characterization of an IL-12 p40/p35 Truncated Fusion Protein That can Inhibit the Action of IL-12." Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.. 2015 Sep 0; 35(9):690-7. Epub 2015 May 04.

6/25/2015
Mikucki ME, Fisher DT, Matsuzaki J, Skitzki JJ, Gaulin NB, Muhitch JB, Ku AW, Frelinger JG, Odunsi K, Gajewski TF, Luster AD, Evans SS. "Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints." Nature communications. 2015 Jun 25; 6:7458. Epub 2015 Jun 25.

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